The goal of the research is to determine the power and the feasibility of the study design and methods to inform a full-scale clinical trial that will determine whether treatment of obstructive sleep apnea in older adults with mild cognitive impairment delays cognitive decline and preserves everyday function.

Hopkins Verbal Learning Test-Revised [HVLT-R] [ Time Frame: Change from baseline at 6 months for both arms and again at 1 year for the active arm ] [ Designated as safety issue: No ]

Memory (immediate and delayed recall) will be assessed using HVLT-R. HVLT-R has been used in elders with Alzheimer's Disease and takes 10 minutes to complete. We will use 6 alternative forms. Forms 1, 2, and 4 will be used for half the participants and forms 3, 5 and 6 will be used for the rest of the participants.

Everyday Cognition [E-Cog] [ Time Frame: Change from baseline at 6 months for both arms and again at 1 year for the active arm ] [ Designated as safety issue: No ]

Cognitively mediated functional abilities will be assessed using E-Cog. It is a study-partner rated 39-item questionnaire.

Secondary Outcome Measures:

Digit Symbol-Coding [DSC] [ Time Frame: Change from baseline at 6 months for both arms and again at 1 year for the active arm ] [ Designated as safety issue: No ]

Psychomotor/cognitive processing speed will be assessed using the DSC subtest from the Wechsler Adult Intelligence Test (WAIS-III).

Mini Mental State Exam (MMSE) [ Time Frame: Change from baseline at 6 months for both arms and again at 1 year for the active arm ] [ Designated as safety issue: No ]

Global cognitive function will be assessed using MMSE. It is a 30-item cognitive screen measuring orientation, registration, short-term memory, attention/concentration, language, and constructional capacity. Summary score will be used as a measure of global cognitive function. It takes about 5 minutes to complete.

Stroop Color and Word Test [SCW] [ Time Frame: Change from baseline at 6 months for both arms and again at 1 year for the active arm ] [ Designated as safety issue: No ]

Attention will be measured using SCW. We will use the Golden format, which is sensitive to age-related declines in processing speed. The SCW has been used in elders with Alzheimer's Disease and it takes about 30 minutes to complete.

The Psychomotor Vigilance Task (PVT) [ Time Frame: Change from baseline at 6 months for both arms and again at 1 year for the active arm ] [ Designated as safety issue: No ]

Attention/reaction time will assessed using the PVT. PVT has been used in elders with Alzheimer's Disease and requires about 30 minutes to complete.

Epworth Sleepiness Scale [ESS] [ Time Frame: Change from baseline at 6 months for both arms and again at 1 year for the active arm ] [ Designated as safety issue: No ]

Daytime sleepiness be assessed using ESS. The ESS asks the respondent to rate the likelihood of falling asleep in eight specific situations using a four-point Likert scale ranging from never dozing to high chance of dozing. The scale significantly correlates with the frequency of apneas and is a clinical and research standard for the assessment of daytime sleepiness. Persons with cognitive impairment are able to complete the scale. It requires 5 minutes to complete.

Functional Outcomes Sleep Questionnaire [FOSQ] [ Time Frame: Change from baseline at 6 months for both arms and again at 1 year for the active arm ] [ Designated as safety issue: No ]

Everyday function will be assessed using FOSQ. It is a 30-item Likert-scale, self-report, disease-specific functional status measure written at the 4th grade level.

Global change (progression) will be assessed using ADCS-CGIC at 1 year. It can be completed at home by participants or their study partners. It is sensitive to small differences in several domains that may add up to a clinically meaningful change.

Clinical Dementia Rating Scale [CDR] [ Time Frame: Change from baseline at 1 year for the active arm ] [ Designated as safety issue: No ]

Cognitive ability will be assessed and staged using CDR. It uses a structured interview takes 60-90 minutes to complete. The CDR will be completed by the graduate assistant with input from the geriatrician and neuropsychologist.

Change in hippocampal volume between baseline and 1 year follow-up scan (atrophy) will be quantified automatically using unbiased registration between 2 time points. Structural and calibration scans used in this protocol have been adopted from the Alzheimer's Disease Neuroimaging Initiative [ADNI] protocol.

Structural effects of CPAP outside of the hippocampus will be measured using FreeSurfer software to automatically estimate hemispheric and lobar cortical thickness; cortical and subcortical gray matter volume; white matter volume; and ventricular volume. The FreeSurfer longitudinal module will be used to estimate change in these measures.

We will perform automatic segmentation of hippocampal subfields in the baseline T2-weighted turbo spin echo [TSE] images. This will estimate volumes of subfields CA1, CA2, CA3, dentate gyrus, subiculum, and entorhinal cortex. We will then quantify longitudinal change in subfield volumes using the approach for the whole hippocampus, modified to account for anisotropic voxel size in TSE images.

The volume of white matter hyperintensity (leuokoaraiosis) will be assessed in CSFsuppressed T2-weighted (FLAIR) structural MRI. A semi-automated intensity-based segmentation technique will be used to identify cortical and subcortical strokes as well as ischemic lesions in subcortical white matter considered to be the sequelae of hypoperfusion.

Study participants will be randomized to receive either active continuous positive airway pressure (CPAP) or sham CPAP for 6 months. Dosage of active CPAP will be individually determined using standardized methods in an overnight CPAP titration polysomnography. At the end of 6 months those in the sham group will receive active CPAP and be discharged from the study. Those assigned to the active CPAP group will participate in an open label study for 6 additional months.

Active Comparator: Active Continuous Positive Airway Pressure

Device: Continuous Positive Airway Pressure [CPAP]

Study participants will be randomized to receive either active continuous positive airway pressure (CPAP) or sham CPAP for 6 months. Dosage of active CPAP will be individually determined using standardized methods in an overnight CPAP titration polysomnography. At the end of 6 months those in the sham group will receive active CPAP and be discharged from the study. Those assigned to the active CPAP group will participate in an open label study for 6 additional months.

Detailed Description:

We propose to conduct a 6-month double-blind randomized, placebo-controlled pilot clinical trial to compare the effects of active continuous positive airway pressure versus sham continuous positive airway pressure on cognitive and everyday function in 110 older adults with mild cognitive impairment and obstructive sleep apnea. We also will collect pilot data on the 1-year outcomes of treatment of obstructive sleep apnea, and the validity of neuroimaging for measuring clinical change in persons with mild cognitive impairment and obstructive sleep apnea. The results will inform the study design, sample size, participant recruitment and retention methods, and measures for a full-scale trial.

Eligibility

Ages Eligible for Study:

55 Years to 89 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria

Participants are included in the study if all of the following criteria are met:

Are able to provide written informed consent by self or legally authorized representative. MacArthur Competency Assessment Tool [MacCAT-CR] will be used to assess decision making capacity

Moderate to severe obstructive sleep apnea (OSA) as deﬁned by an apnea-hypopnea index (AHI) >= 15 using either the Apnea Risk Evaluation System (ARES) OR diagnostic polysomnography as a screening measure

Psychiatric disorders, including major depression or bipolar disorder based on DSM-IV diagnostic criteria within the past 3 months, psychotic features, agitation or behavioral problems within the last 3 months that could lead to difficulty complying with the protocol, or history of schizophrenia (also by DSM-IV criteria)

History of alcohol abuse or dependence within the past 2 years (DSM-IV criteria)

Any current signiﬁcant systemic illness or unstable medical condition that could lead to difficulty in complying with the protocol (bronchospasm or symptomatic chronic obstructive pulmonary disease as indicated by regular use of bronchodilators, steroids, history of carbon dioxide retention, waking hypoxemia, or use of supplemental oxygen; uncontrolled thyroid disease, diabetes, or seizure disorder; cirrhosis; recently diagnosed cancer; clinically signiﬁcant laboratory abnormalities such as B12)

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01482351